Mechanistic considerations on the azepine-ring formation through the ene reactions at the periphery of heterocyclic systems

Abstract

A mechanistic proposal for the azepine-ring formation at the periphery of heterocyclic systems is described. Intramolecular thermal ene reactions of O-alkyl oximes 5 and 6, N′, N′-disubstituted hydrazone 11, and N-tosyl imines, obtained from aldehydes of pyrido[1,2- a]pyrimidine 1, pyridine 2, and pyrimidine system 3, have been developed. These reactions reveal to be a fruitful and stereoselective approach to the azepine derivatives fused by heterocycles. The mechanistic discussions on the azepine-ring formation through the imine and carbonyl ene reactions have been accomplished by the kinetic studies as well as the molecular orbital calculations (PM3 method) of the model reactions. These results demonstrate that both ene reactions proceed in a concerted manner.